Characterization of HIV type 1 gp120 V3 region sequences from Ugandan infants.
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Amino Acid Sequence↗
Biomedical subjects
P Kataaha
Publications and source records attributed to P Kataaha.
Lack of efficacy of low dose oral interferon alfa in symptomatic HIV-1 infection: a randomised, double blind, placebo controlled trial.
BACKGROUND: Interferon alfa (IFN-alpha) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-alpha concentrations > or = 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-alpha resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the efficacy of this treatment persisted. METHODS: We studied 559 adult Ugandan patients with WHO stage 2-4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-alpha/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrollment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study. RESULTS: Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-alpha group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 x 10(6)/l) than the placebo group (median 85.3 x 10(6)/l) (p = 0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-alpha and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-1 seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-alpha activity. CONCLUSIONS: The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-alpha/day in a population of African patients with symptomatic HIV infection.
Acquired Immunodeficiency Syndrome↗
Rapid HIV testing with same-day results: a field trial in Uganda.
Rapid, on-site HIV testing with same-day results may improve services and increase the number of clients who learn their serostatus in developing countries. To validate test performance under field conditions and assess the change in the proportion of clients who learn their serostatus, we conducted a field trial using the Capillus HIV-1/HIV-2 assay (Cambridge Diagnostics) at the AIDS Information Centre counselling and testing sites in Uganda. Compared to the standard 2-EIA testing algorithm, the sensitivity of Capillus was 99.6% (95% CI; 98.5%, 99.9%), the specificity was 98.8% (95% CI; 98.1%, 99.3%), the positive predictive value was 96.5% (95% CI; 94.5%, 97.8%), and the negative predictive value was 99.9% (95% CI; 99.5%, 100%). It took less than 5 min to perform a single test, and results were returned to clients in less than an hour, during which time clients were counselled. This resulted in a 27% increase in the proportion of clients who learned their serostatus and received counselling. We conclude that simple, rapid HIV tests can be performed accurately on-site within the time frame of a clinic visit, increasing the number of clients who learn their serostatus and receive post-test counselling.
HIV Infections↗
Detection of human immunodeficiency virus type 1 (HIV-1) DNA and RNA sequences in HIV-1 antibody-positive blood donors in Uganda by the Roche AMPLICOR assay.
The ability of commercially available PCR-based assays to accurately detect or quantitate human immunodeficiency virus type 1 (HIV-1) DNA or RNA in individuals predominantly infected with HIV-1 subtypes A and D is not known. Therefore, peripheral leukocytes from 43 individuals in Kampala, Uganda, positive for HIV by the Western blot (immunoblot) assay were tested by using the Roche AMPLICOR HIV-1 assay for the detection of DNA gag sequences. Plasma from these same individuals was tested by using the Roche HIV-1 AMPLICOR MONITOR HIV-1 assay for the quantitation of HIV-1 RNA gag sequences. In addition, peripheral leukocytes were tested for HIV-1 DNA by using a lower annealing temperature or a different primer pair for the HIV-1 pol region. The proportions of individuals with detectable HIV-1 DNA and RNA gag sequences by the Roche assays were 74 and 90%, respectively. The proportions positive for HIV-1 DNA sequences by using a 50 degrees C annealing temperature or the pol primer pair were 71 and 98%, respectively. In summary, the standard Roche assay did not detect HIV-1 DNA sequences in a significant number of HIV-1-infected individuals in Uganda. However, use of a pol primer pair increased the sensitivity of the assay to 98%. The sensitivity of the Roche AMPLICOR MONITOR assay for the detection and quantitation of HIV-1 RNA sequences was significantly higher than that of the DNA-based assay, but the efficiency of the assay, and hence, the accuracy of the values obtained with RNA, is not known. Modifications to existing assays are needed to enhance the sensitivities and accuracies of these commercially available assays for use in developing countries where non-B HIV-1 subtypes predominate.
DNA, Viral↗
Comparison of saliva and serum for human immunodeficiency virus type 1 antibody testing in Uganda using a rapid recombinant assay.
The accuracy and acceptability of saliva human immunodeficiency virus type 1 (HIV-1) antibody testing were compared with serum testing in a study of paired specimens from HIV-1-seropositive and HIV-1-seronegative Ugandan adults attending a clinic for sexually transmitted diseases. Saliva collection was performed with the Omni-sal device (Saliva Diagnostic Systems, Vancouver, Wash.), and antibody testing was performed by a rapid filter paper assay (Test-Pack; Abbott Laboratories, Abbott Park, Ill.). Relative to serum testing, the sensitivity of saliva testing was 95% (195 of 205) and the specificity was 99% (295 of 297). The sensitivity of saliva testing was higher for patients with elevated levels of beta-2 microglobulin in sera and greater numbers of HIV-1-related symptoms. Pre- and poststudy interviews indicated that saliva testing did not foster inordinate fears of saliva exposure. The development of saliva tests that are inexpensive and do not require electricity is needed.
Adult↗
Detection of human immunodeficiency virus type 1 (HIV-1) DNA and p24 antigen in breast milk of HIV-1-infected Ugandan women and vertical transmission.
OBJECTIVE: To determine the correlation between the detection of human immunodeficiency virus type 1 (HIV-1) in breast milk, the duration of breastfeeding, and vertical transmission of HIV-1 infection in Ugandan women. METHODS: A prospective study of HIV-1 infection in pregnant Ugandan women and their infants has been ongoing since 1990 with follow-up of mother-infant pairs for at least 2 years. Expressed breast milk specimens were collected from 201 HIV-1-seropositive and 86 HIV-1-seronegative Ugandan women approximately 6 weeks after delivery. The presence of HIV-1 DNA in the cellular fraction of the breast milk was detected by polymerase chain reaction (PCR), and HIV-1 p24 antigen was detected in the cell-free breast milk supernatant using p24 antigen enzyme immunoassay (EIA) after immune complex dissociation (ICD). The duration of breastfeeding and the clinical status of the mothers and their children were recorded. HIV-1 EIA, Western blot, PCR, or p24 antigen detection were used for the determination of the HIV-1 infection status of the children. RESULTS: Of the 201 HIV-1-infected women studied, 47 had HIV-1-infected children, 143 had children who seroreverted, and 11 had children of indeterminate status. Breast milk supernatants were available for ICD p24 antigen testing from 188 of the HIV-1-infected women and none had detectable p24 antigen. Breast milk cell pellets were available and contained amplifiable DNA in 125 of the HIV-1-infected women (20 transmitters, 104 nontransmitters, 1 indeterminate). HIV-1 DNA was detected by PCR in 72% (75/104) of nontransmitters and 80% (16/20) of the transmitters. The duration of breastfeeding by transmitter mothers (15.8 months) was not significantly different from nontransmitter mothers (14.4 months). CONCLUSIONS: No correlation was found between the detection of HIV-1 in breast milk or the duration of breastfeeding and transmission of HIV-1 infection in this study of Ugandan women.
Breast Feeding↗
Relative reactivity of the V3 loop PND of HIV-1 subtypes A, B, C, D, and F with sera from selected Ugandan localities.
Synthetic peptides comprising the predicted principal neutralizing determinant (PND) in new African and North American HIV-1 clones were tested in ELISA for reactivity with ninety six serum samples from asymptomatic donors in six selected localities in Uganda. Irrespective of the geographical origin of the samples, the majority of the test sera cross-reacted at high intensities with the peptides derived from the North American clone, BRT3.6 (Group B), the Ugandan clone, CUG045, (Group C), and the Romanian clone, FRMA (Group F). The frequency of reactivity of the peptides from BRT3.6, CUG045, and FRMA were within the ranges of 57-100%, 50-100%, and 57-100%, respectively, for the sera collected from these disparate localities. In contrast to these findings, the V3 peptides derived from the other Ugandan isolates showed a more restricted pattern of reactivity with the same serum samples: AUG06c (1-63%), DUG23c (2%), and DUG044 (38-87%). The results from ELISA inhibition assay indicated that the V3 peptide from BRT 3.6, CUG045, and FRMA express closely related antigenic specificities quite distinct from those in AUG06c and DUG044. The residues comprising the PND in BRT 3.6, CUG045, and FRMA appear to be well conserved in the HIV-1 subtypes prevalent in the selected Ugandan locales.
Amino Acid Sequence↗
Second generation hepatitis C virus assays: performance when testing African sera.
Sera were collected from 426 volunteers in Uganda at high and low risk for acquisition of hepatitis C virus (HCV). All samples were tested by the Ortho HCV second generation ELISA (S1) and by the INNOTEST HCV Ab second generation enzyme immunoassay, (S2), (Innogenetics, Antwerpen, Belgium). Sera that were repeatedly reactive by either screening assay were further tested by each of two different HCV supplemental/confirmatory assays: a second generation recombinant immunoblot assay (RIBA, Ortho Diagnostics), (C1), and a line immunoassay (INNO-LIA HCV-Ab, Innogenetics), (C2). In these populations there were 16 true positives, 351 true negatives, and 59 indeterminate results. Fifty-nine point four percent (253/426) of the samples were repeatedly reactive by the S1 test, while only 2.6% (11/426) were repeatedly reactive by S2. Test S1 produced a high false positive rate, a low positive predictive value, a specificity of 49.3%, and had a sensitivity of 100%. In contrast, the S2 screening assay had much higher specificity (98.8%), but lacked in sensitivity (31.3%). This poor sensitivity of S2 was based almost exclusively on the fact that the C2 supplemental test classified 9 samples as confirmed positive when the homologous screening assay classified these samples as negative; several of these were not confirmed when using a new generation INNO-LIA. Both the screening tests S1 and S2, and the supplemental assays C1 and C2 exhibited a significant degree of discordance, and neither of the screening tests alone would be adequate for use in these populations.
Adult↗
A rapid manual method for CD4+ T-cell quantitation for use in developing countries.
OBJECTIVE: To evaluate a manual method (Cytosphere) for quantifying CD4+ T-cell numbers. DESIGN: Cross-sectional study of HIV-1-seronegative and HIV-1-seropositive individuals evaluated for absolute CD4 counts by both standardized flow cytometric measurements and manual Cytosphere technology using a hemacytometer. SETTING: University research hospitals in both the United States and Africa. PATIENTS, PARTICIPANTS: Blood specimens from 382 patients were evaluated. These were broken down into 294 samples obtained from HIV-1-seropositive patients and 88 samples obtained from HIV-1-seronegative patients. INTERVENTIONS: None. OUTCOME MEASURED: Absolute CD4 cell number. RESULTS: Evaluation of samples obtained from HIV-1 patients in both the United States and Africa demonstrated an overall correlation of the Cytosphere assay with flow cytometry of 0.912 (95% confidence interval, 0.895-0.928; P < 0.001). When samples were stratified based on CD4+ T-cell counts determined by flow cytometry, the Cytosphere assay had a 96% predictive value for correctly identifying individuals with CD4 T-cell counts > 200 x 10(6)/l and a 92% predictive value for correctly identifying individuals with CD4 T-cell counts < 200 x 10(6)/l. CONCLUSIONS: This assay appears to have the potential for the quantitation of CD4 cells in the limited laboratory facilities in developing countries and to have a strong correlation with standard flow cytometric technology.
Adult↗
Beta 2-microglobulin, HIV-1 p24 antibody and acid-dissociated HIV-1 p24 antigen levels: predictive markers for vertical transmission of HIV-1 in pregnant Ugandan women.
OBJECTIVES: To evaluate the clinical utility of plasma beta 2-microglobulin (beta 2M) levels, acid-dissociated HIV-1 p24 antigen, and HIV-1 p24-antibody titers in predicting HIV-1 vertical transmission in 227 HIV-1-infected Ugandan pregnant women. DESIGN: Plasma beta 2M levels, acid-dissociated HIV-1 p24-antigen positivity, and HIV-1 p24-antibody titers were determined using commercial enzyme immunoassays (EIA) in a Ugandan cohort of 52 HIV-1-seropositive transmitting mothers, 175 HIV-1-seropositive non-transmitting mothers, and 52 seronegative mothers within 6 weeks prior to delivery. RESULTS: Transmitter mothers had significantly higher plasma concentrations of beta 2M (1.80 +/- 1.13 mg/l) than non-transmitter seropositive mothers (1.32 +/- 0.81 mg/l; P = 0.0013). Similarly, a significantly higher proportion of transmitter mothers had detectable p24 antigen than non-transmitter mothers [six out of 51 (11.8%) versus six out of 173 (3.5%); P = 0.03]. Compared with the vertical transmission rate of 23% in the seropositive group, the positive predictive values of a beta 2M level > 1.5 mg/l or detectable HIV-1 p24 antigen for vertical transmission were 34 and 50%, respectively. Five of six (83.3%) seropositive mothers with both a beta 2M level > 1.5 mg/l and detectable p24 antigenemia transmitted HIV-1 infection to their infants compared with 25 of 124 (20.2%) seropositive mothers with values below the cut-off values for both tests (P = 0.00249). However, beta 2M was not found to be a significant independent predictor of vertical transmission when analyzed in a multivariate model with p24 antigenemia. There was no significant difference in HIV-1 p24-antibody titers in transmitter mothers versus non-transmitter mothers (P = 0.299). CONCLUSION: beta 2M levels and acid-dissociated HIV-1 p24-antigen assays may be used to predict which HIV-1-infected pregnant women are at greatest risk for vertical transmission. However, only the p24-antigen test was independently predictive of vertical transmission and its clinical utility is limited.
Adolescent↗
Plasma viral load in symptom-free women and vertical transmission of HIV-1.
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Acquired Immunodeficiency Syndrome↗
HIV prevalence, attitudes and behaviour in clients of a confidential HIV testing and counselling centre in Uganda.
OBJECTIVE: To describe clients, operation and impact of an African public HIV testing and counselling centre. DESIGN AND SETTING: Analysis of samples from clients attending the AIDS Information Centre (AIC) in Kampala, Uganda in early 1991. SUBJECTS: HIV-1-positive and HIV-negative consecutive clients (250 of each), 86 consecutive couples, and 200 consecutive clients who were HIV-negative in 1990 and were attending for their repeat test. MAIN OUTCOME MEASURES: HIV seroprevalence rates, attitudes, behaviour and behaviour change. RESULTS: HIV-1 prevalence was 28% overall, 24% in men and 35% in women. Reasons for taking the HIV test were a planned marriage or a new relationship (27%; 84% in couples), to plan for the future (35%), distrust of sexual partner (14%) and illness or disease/death (not HIV-specific) of partner (20%). The majority of the reported intentions in response to a positive or a negative HIV test result were positive, demonstrating the ability to cope with this information. Of repeat clients, two (1%) had become HIV-1-positive. The majority of repeat clients reported one sexual partner only (67%) or sexual abstinence (25%). Compared with pre-test information from AIC clients attending for the first time, repeat clients reported casual sexual contacts less often (6 versus 25%) and, of those, the majority used condoms. CONCLUSIONS: Our study demonstrates the demand for and the feasibility of confidential HIV testing and counseling services in Uganda, and illustrates the value of these services in achieving behaviour changes. Such services should be considered an additional approach for the reduction of HIV transmission in Africa, especially in areas with high HIV seroprevalence rates.
Acquired Immunodeficiency Syndrome↗
Hepatitis C virus antibody in HIV-1 infected Ugandan mothers.
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Female↗
Non-isotopic polymerase chain reaction methods for the detection of HIV-1 in Ugandan mothers and infants.
Two non-isotopic polymerase chain reaction (PCR) methods were evaluated by testing blood from 41 HIV-1-seropositive and 16 HIV-1-seronegative Ugandan mothers and 56 of their children (aged 0.5-15.0 months). Amplification of HIV-1 sequences was performed in duplicate using a biotinylated primer pair to the gag region (SK 462-431) and nested primer pairs (JA 17-20) to the pol region of HIV-1. gag sequences were hybridized using a microtiter plate coated with the SK 102 probe followed by colorimetric detection using an avidin-horseradish peroxidase conjugate and tetramethylbenzidine/peroxide substrate. pol sequences were detected on agarose gel stained with ethidium bromide. Results of HIV-1 PCR analysis showed that 40 out of 41 (98%) seropositive mothers and 10 out of 29 (34%) seropositive children had detectable HIV-1 gag and pol sequences. None of the 16 seronegative mothers nor 27 seronegative or Western blot-indeterminate children had detectable HIV-1 sequences. Our results suggest that non-isotopic PCR methods are sensitive, specific, and potentially useful in the early diagnosis of HIV-1 infection in developed and developing countries.
Adolescent↗
Risk factors for the spread of AIDS in rural Africa: evidence from a comparative seroepidemiological survey of AIDS, hepatitis B and syphilis in southwestern Uganda.
Before commencing rational control programmes for AIDS in Africa it is desirable to determine the relative importance of heterosexual and various non-sexual modes of transmission. We investigated this by comparing the seroepidemiologies of AIDS, hepatitis B and syphilis at two rural hospitals in southwest Uganda. During August 1986, 3% of 357 outpatients, reflecting the age and sex composition of the general population, were anti-HIV positive. Anti-HIV seropositivity, both in the outpatients and among 36 suspected prostitutes and 14 suspected AIDS cases, was confined to individuals aged 20 or over. For men, seropositivity was associated with sexual contact with prostitutes (a risk factor for 61% of young men in the study). In the prostitute group, 25% were anti-HIV positive and 46% were positive on the Treponema pallidum haemagglutination (TPHA) test for syphilis. The risk factors for HIV, but not hepatitis B, were the same as for having a history of sexually transmitted disease (STD). However, there was, surprisingly, an association between a history of STD and seropositivity for hepatitis B virus but not for HIV infection. The geographical and age distributions of seropositivity for HIV and hepatitis B virus were also quite different. Finally, blood transfusions, scarification and exposure to mosquitoes (as assessed by a history of malaria) were not evident risk factors for either HIV or hepatitis B virus. AIDS in rural Africa seems to differ in its epidemiology from hepatitis B and appears to be spread predominantly by pre-existing patterns of heterosexual activity responsible for high rates of other sexually transmitted diseases.
AIDS Serodiagnosis↗
HIV infection through normal heterosexual contact in Uganda.
One hundred and fourteen household contacts of 23 patients with AIDS or suspected AIDS were examined for evidence of infection with HIV. In total 12 contacts had antibodies to the virus by a competitive enzyme-linked immunosorbent assay (ELISA), confirmed by Western blot. Ten of these seropositive contacts were the sexual partners of the index cases. Overall 71% of sexual partners (10:14) were seropositive. By contrast only 2:100 of the non-sexual contacts had evidence of infection. These were the daughter of an index case and her 2-year-old son who were seropositive but had their own independent risk factors. The data presented here support the hypothesis that a major route of transmission of HIV in an African population is through heterosexual contact and furthermore suggest that transmission by other means such as intimate non-sexual contact, insect vectors, or the use of non-sterile needles is much less important.
Acquired Immunodeficiency Syndrome↗
Human monoclonal antibodies from patients with rheumatoid arthritis: cross reactions against cellular constituents.
Hybridization of peripheral blood lymphocytes from patients with rheumatoid arthritis has yielded 14 monoclonal antibodies which react with cultured human epithelial cells. Immunofluorescence staining identifies at last five different types of antibody. Solid phase immunosorbent assays show a variety of cross-reaction patterns with nucleic acids, proteoglycan, cardiolipin and plastic, confirming that the various antibodies react with epitopes which are at least slightly different. These conclusions are confirmed by SDS gel electrophoresis and immunoblotting on epithelial cell extracts. Similar antibodies previously found in association with lupus-like disease have been thought to be representative of the high antinuclear antibody response characteristic of lupus. Our data are more consistent with the hypothesis that all or many of these antibodies are part of the normal inflammatory response.
Antibodies, Monoclonal↗